Fluvastatin, of which the full chemical name is R*, S*-(E)-(.+-.)-7-[3-(4-fluorophenyl)-1-(1-methyl-ethyl)-1H-indol-2-yl]-3,5- dihydroxy-6-heptenoic acid, as well as its sodium salt, are disclosed in EP-A-0 114 027. Fluvastatin is an inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, which is a key enzyme in the regulation of cholesterol biosynthesis. Fluvastatin can be used pharmaceutically particularly as a hypercholesterolemic, hyperlipoproteinemic and antiatherosclerotic agent Fluvastatin sodium recovered by lyophilization is disclosed in U.S. Pat. No. 4,739,073.
In EP-A-0 547 000 it is disclosed that fluvastatin sodium is extremely susceptible to degradation at pH below about 8. The suggested solution is to provide compositions comprising the drug substance and an alkaline medium, which is capable of by imparting a pH of at least 8 to an aqueous solution or dispersion of the composition. ##STR1##
It is pointed out in EP-A-547 000 that, in addition to the pH sensitivity, the heat and light sensitivity, as well as the hygroscopicity, of fluvastatin sodium impose particular requirements on the manufacture and storage of pharmaceutical dosage forms of fluvastatin sodium. It is known in the art that lower hygroscopicity will lead to improved chemical stability and longer shelf life of chemical compounds.
Consequently, there is a need for new forms of fluvastatin sodium having improved chemical stability, making possible the preparation of pharmaceutical formulations of fluvastatin sodium with less need for stabilizing agents and with prolonged shelf life, and with the possibility of being provided in less sophisticated packages.